The ability of certain inbred mouse strains to produce high titers of IgE and IgG antibodies to limiting doses of antigen plus adjuvants is under genetic control. An important feature of the immune responses produced to these antigens, is their strong dependence on interactions between T and B lymphocytes whose specificity is controlled strictly by genes which map within the major histocompatibility complex region probably because of the region's profound effect on cell plasma membranes. This project considers the possibility that pharmacologic mechanisms affect the products of lymphoid cell interactions, at least as far as humoral immunity is concerned. Thus, the antigen-induced release of mediators, principally histamine, from sensitized mast cells may regulate specific immune responses through a dual mechanism. First, histamine promotes the contact of antigen molecules with lymphoid cells by increasing the lymphatic drainage of the areas where antigen appears. Second, histamine may inhibit the response of specific immunocompetent cells to antigen via increases in cyclic AMP levels. Pertinent to this question is the observation currently studied by the project's principal investigator, that spleen cells of inbred mouse strains immunized with limiting doses of ovalbumin plus aluminum hydroxide exhibit altered sensitivities to cyclic AMP elevations induced by histamine. Experiments will be performed to evaluate the importance that antigen and/or adjuvant play in the apparent increases in histamine receptors and to identify the types of lymphoid cells where histamine receptor changes occur. Such experiments should contribute to the understanding of the development in vivo of immune responses.